Immunocompromised individuals and those with lung dysfunction readily acquire pulmonary bacterial infections, which may cause serious diseases and carry a heavy economic burden. Maintaining adequate ...antibiotic concentrations in the infected tissues is necessary to eradicate resident bacteria. To specifically deliver therapeutics to the infected pulmonary tissues and enable controlled release of payloads at the infection site, a ROS-responsive material, i.e. 4-(hydroxymethyl) phenylboronic acid pinacol ester-modified α-cyclodextrin (Oxi-αCD), was employed to encapsulate moxifloxacin (MXF), generating ROS-responsive MXF-containing nanoparticles (MXF/Oxi-αCD NPs).
MXF/Oxi-αCD NPs were coated with DSPE-PEG and DSPE-PEG-folic acid, facilitating penetration of the sputum secreted by the infected lung and enabling the active targeting of macrophages in the inflammatory tissues. In vitro drug release experiments indicated that MXF release from Oxi-αCD NPs was accelerated in the presence of 0.5 mM H
O
. In vitro assay with Pseudomonas aeruginosa demonstrated that MXF/Oxi-αCD NPs exhibited higher antibacterial activity than MXF. In vitro cellular study also indicated that folic acid-modified MXF/Oxi-αCD NPs could be effectively internalized by bacteria-infected macrophages, thereby significantly eradicating resident bacteria in macrophages compared to non-targeted MXF/Oxi-αCD NPs. In a mouse model of pulmonary P. aeruginosa infection, folic acid-modified MXF/Oxi-αCD NPs showed better antibacterial efficacy than MXF and non-targeted MXF/Oxi-αCD NPs. Meanwhile, the survival time of mice was prolonged by treatment with targeting MXF/Oxi-αCD NPs.
Our work provides a strategy to overcome the mucus barrier, control drug release, and improve the targeting capability of NPs for the treatment of pulmonary bacterial infections.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Coded caching schemes with low subpacketization and small transmission rate are desirable in practice due to the requirement of low implementation complexity and efficiency of transmission. Placement ...delivery arrays (PDA in short) can be used to generate coded caching schemes. However, many known coded caching schemes, which have low subpacketizations, realized by PDAs do not fully use the users' caching content to create multicasting opportunities. So we propose a method to overcome this drawback. As an application, we obtain a new scheme, which has significantly advantages on the tradeoff between memory ratio and transmission rate.
An alkaline-earth metal catalytic system for environmentally benign allylic alkylation was developed. Allylic alcohols can be utilized directly at room temperature in this transition-metal-free ...process, producing water as the only byproduct. A variety of allylic compounds, including the ones containing all-carbonyl quaternary centers, can be obtained with high yields.
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IJS, KILJ, NUK, PNG, UL, UM
The regulation of skeletal muscle growth and development in chicken is complex. MicroRNAs (miRNAs) have been found to play an important role in the process, and more research is needed to further ...understand the regulatory mechanism of miRNAs. In this study, leg muscles of Jinghai yellow chickens at 300 d with low body weight (slow-growing group) and high body weight (fast-growing group) were collected for miRNA sequencing (miRNA-seq) and Bioinformatics analysis revealed 12 differentially expressed miRNAs (DEMs) between the two groups. We predicted 150 target genes for the DEMs, and GO and KEGG pathway analysis showed the target genes of miR-24-3p and novel_miR_133 were most enriched in the terms related to growth and development. Moreover, networks of DEMs and target genes showed that miR-24-3p and novel_miR_133 were the 2 core miRNAs. Hence, miR-24-3p was selected for further functional exploration in chicken primary myoblasts (CPMs) with molecular biology technologies including qPCR, cell counting kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU) and immunofluorescence. When proliferating CPMs were transfected with miR-24-3p mimic, the expression of cyclin dependent kinase inhibitor 1A (P21) was up-regulated and both CCK-8 and EdU assays showed that the proliferation of CPMs was inhibited. However, when the inhibitor was transfected into the proliferating CPMs, the opposite results were found. In differentiated CPMs, transfection with miR-24-3p mimic resulted in up regulation of MYOD, MYOG and MYHC after 48 h. Myotube areas also increased significantly compared to the mimic negative control (NC) group. When treated with inhibitor, differentiation CPMs produced the opposite effects. Overall, we revealed 2 miRNAs (novel_miR_133 and miR-24-3p) significantly related with growth and development and further proved that miR-24-3p could suppress the proliferation and promote differentiation of CPMs. The results would facilitate understanding the effects of miRNAs on the growth and development of chickens at the post-transcriptional level and could also have an important guiding role in yellow-feathered chicken breeding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction
Immune checkpoint inhibitors have made tremendous progress over the last decade in the treatment of cutaneous melanoma, but their application in uveal melanoma treatment is less ...successful, owing in part to the immunological privilege of the eye and the liver, the most frequent site of metastasis. Nevertheless, the therapeutic outcomes reported currently are less pessimistic.
Methods
In this review, we provide an overview of recent studies of immune checkpoint inhibitors in uveal melanoma and its metastasis and classify studies in this field into three groups: monotherapy of immune checkpoint inhibitors, dual-agent immune checkpoint inhibitors, and immune checkpoint inhibitors combined with other systemic or regional therapies.
Results
Briefly, monotherapy with immune checkpoint inhibitors performed poorly. Dual-agent immune checkpoint inhibitors had slightly better outcomes than traditional treatments, especially in specific patient populations. As for the combination therapy, the combination with other systemic therapies did not show superiority over dual-agent immune checkpoint inhibitors, but combination with hepatic regional therapies was quite promising. Moreover, research on emerging checkpoints is currently limited to the stage of mechanistic studies.
Conclusion
We propose that immune checkpoint inhibitors remain alternative treatments for patients with uveal melanoma, but factors such as cost-effectiveness should also be taken into account. The combination therapy with immune checkpoint inhibitors deserves to be further explored.
Abstract
The gait of Amur tiger was studied through video images, and a more accurate individual recognition system of Wild Amur tiger was given on the premise of supplementing pattern recognition ...technology. Through further research on the common gait of Amur tiger, the basic information database was established to realize the physiological state research of Amur tiger. The characteristic structure and movement standard model of Amur tiger were constructed to complete the simulation and reconstruction of Amur tiger’s routine movement. Through the simulation corridor of tiger movement trajectory, the ecological protection area can be divided effectively.
Previous research has extended the stress literature by exploring the relationship between family incivility and cyberbullying perpetration, yet relatively less attention has been paid to underlying ...psychological mechanisms between that relationship among university students. According to the Frustration-Aggression Theory, this study examined the relationships of family incivility, cyberbullying perpetration, negative emotions and neuroticism among Chinese university students. Data were collected from 814 university students (females,
N
= 423; Mage = 19.96 years, SD = 3.09). The results examined the mechanism through which family incivility was significantly related to cyberbullying perpetration through the mediation of negative emotions, suggesting a strong link of stressful life events to online aggression. In addition, high levels of neuroticism moderated the relationship between family incivility and cyberbullying perpetration, as well as that between family incivility and negative emotions. The study revealed the chronic and potential impact of family incivility, underlined the interaction between stressful life events and online aggression, and put forward the intervention strategies of cyberbullying among university students.
Neoantigens derived from somatic DNA alterations are ideal cancer-specific targets. In recent years, the combination therapy of PD-1/PD-L1 blockers and neoantigen vaccines has shown clinical efficacy ...in original PD-1/PD-L1 blocker non-responders. However, not all somatic DNA mutations result in immunogenicity among cancer cells and efficient tools to predict the immunogenicity of neoepitopes are still urgently needed. Here, we present the Seq2Neo pipeline, which provides a one-stop solution for neoepitope feature prediction using raw sequencing data. Neoantigens derived from different types of genome DNA alterations, including point mutations, insertion deletions and gene fusions, are all supported. Importantly, a convolutional neural network (CNN)-based model was trained to predict the immunogenicity of neoepitopes and this model showed an improved performance compared to the currently available tools in immunogenicity prediction using independent datasets. We anticipate that the Seq2Neo pipeline could become a useful tool in the prediction of neoantigen immunogenicity and cancer immunotherapy. Seq2Neo is open-source software under an academic free license (AFL) v3.0 and is freely available at Github.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Long noncoding RNAs (lncRNAs) regulate metabolic tissue development and function, including adipogenesis. However, little is known about the function and profile of lncRNAs in intramuscular ...preadipocyte differentiation in chicken. Here, we identified lncRNAs in chicken intramuscular preadipocytes at different differentiation stages using RNA sequencing. A total of 1,311,382,604 clean reads and 25,435 lncRNAs were obtained from 12 samples. In total, 7,433 differentially expressed genes (4,698 lncRNAs and 2,735 mRNAs) were identified by pairwise comparison. These 7,433 differentially expressed genes were grouped into 11 clusters based on their expression patterns by K-means clustering. Using Weighted Gene Coexpression Network Analysis, we identified four stage-specific modules positively related to I0, I2, I4, and I6 stages and two stage-specific modules negatively related to I0 and I2 stages, respectively. Many well-known and novel pathways associated with intramuscular preadipocyte differentiation were identified. We also identified hub genes in each stage-specific module and visualized them in Cytoscape. Our analysis revealed many highly-connected genes, including XLOC_058593, BMP3, MYOD1, and LAMP3. This study provides a valuable resource for chicken lncRNA study and improves our understanding of the biology of preadipocyte differentiation in chicken.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Three novel compounds (1, 2, 3) were obtained from the flower buds of H. citrina.•Twelve known compounds were isolated from Hemerocallis genus for the first time.•Seven compounds ...exhibited NO inhibitory effect in the LPS induced BV2 cells.•Compound 1 play an anti-neuroinflammatory role through MAPK and NF-κB pathway.
Hemerocallis citrina Baroni (H. citrina) has been commonly utilized in diet and conventional medicine. In this study, 21 compounds were obtained from the flower buds of H. citrina. Compounds 1, 2 and 3 were three novel compounds isolated from Hemerocallis genus. Compounds 4, 6, 7, 9, 10, 13–19 were isolated from Hemerocallis genus for the first time. It indicated that compounds 1, 2, 3, 4, 5, 7 and 13 exhibited a significant NO inhibitory effect in the LPS induced BV2 cells. The analysis result of PPI and molecular docking showed that compound 1 may play an anti-neuroinflammatory role through MAPK signaling pathway. The result of pharmacological experiments proved that compound 1 effectively inhibited the generation of NO and inflammatory cytokines by inhibiting the activation of MAPK and NF-κB pathway. This research provided a basis for further study and utilization of H. citrina in anti-neuroinflammatory effect.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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